Glucocorticosteroids are growth-modulating hormones for cells in tissue culture. Often neoplastic transformation alters the cellular response to these hormones. Untransformed 3T3 mouse fibroblasts depend on glucocorticoids for DNA synthesis, while the growth of SV40-transformed 3T3 is inhibited. This research seeks to understand the biochemical mechanism by which these steroids suppress growth in SV3T3 cells. Glucocorticoid action is nontoxic, completely reversible, and is mediated through the cytoplasmic receptor for glucocorticoids. Recent evidence indicates that glucocorticoids create a blockage in G2 of the cell cycle. This conclusion is supported by the observations that DNA synthesis continues long after cell division has ceased, DNA and protein accumulate in dexamethasone-treated cells, and following removal of the steroid cell division resumes and is completed for a majority of the cells within 2 to 4 hours and remains synchronous for two rounds of cell division. Accompanying this G2 block are a number of morphological changes. Under phase contrast the cells appear to round up and to have thickened, darkened centers. In scanning electron micrographs the steroid causes a reduction in the number of microvilli while transmission electron micrographs reveal lead precipitate from the lead citrate stain on the cell surface, suggesting an alteration in the carbohydrate composition of the cell surface. Currently, the possible regulation by glucocorticoids fo glucose-glutamine utilization, insulin binding, and T-antigen expression are being assessed. Although basal glucose uptake is inhibited by dexamethasone, insulin binding increases in response to the steroid. These additional insulin receptors do not seem to be coupled to the glucose transporter, however, since uptake is not stimulated in the presence of insulin. Preliminary results suggest that dexamethasone reduces the expression of SV40 T\antigen, perhaps reflecting a partial alleviation of the transformed state.